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Innate antimicrobial peptide protects the skin from invasive bacterial infection

Nature volume 414, pages 454–457 (2001)Cite this article

Abstract

In mammals, several gene families encode peptides with antibacterial activity, such as the β-defensins and cathelicidins1,2,3. These peptides are expressed on epithelial surfaces and in neutrophils, and have been proposed to provide a first line of defence against infection by acting as ‘natural antibiotics’4,5. The protective effect of antimicrobial peptides is brought into question by observations that several of these peptides are easily inactivated6,7,8 and have diverse cellular effects that are distinct from antimicrobial activity demonstrated in vitro9,10,11,12,13. To investigate the function of a specific antimicrobial peptide in a mouse model of cutaneous infection, we applied a combined mammalian and bacterial genetic approach to the cathelicidin antimicrobial gene family14. The mature human (LL-37)15 and mouse (CRAMP)16 peptides are encoded by similar genes (CAMP and Cnlp, respectively), and have similar α-helical structures, spectra of antimicrobial activity and tissue distribution. Here we show that cathelicidins are an important native component of innate host defence in mice and provide protection against necrotic skin infection caused by Group A Streptococcus (GAS).

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Figure 1: Disruption of the Cnlp gene encoding CRAMP in mice.
Figure 2: Cnlp-deletion renders mice susceptible to severe GAS infection.
Figure 3: GAS mutants resistant to CRAMP produce more severe infections in normal mice.
Figure 4: Cnlp-null mouse blood leukocytes are equivalent in relative number and oxidative burst capacity, but deficient in bacterial killing when compared to leukocytes derived from wild-type mice.

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Acknowledgements

This work was supported by grants from the NIH (R.L. G. and V. N.), a VA merit award (R.L.G.), and grants from the American Skin Association (R.L.G.) and the Rockefeller Brothers Foundation (V.N.).

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Authors and Affiliations

  1. Department of Pediatrics, University of California, San Diego, California, 92161, USA

    Victor Nizet & Richard L. Gallo

  2. Division of Dermatology, University of California, San Diego, 92161, California, USA

    Takaaki Ohtake, Xavier Lauth, Janet Trowbridge, Jennifer Rudisill, Robert A. Dorschner, Vasumati Pestonjamasp & Richard L. Gallo

  3. Veterans Affairs San Diego Healthcare System, San Diego, 92161, California, USA

    Takaaki Ohtake, Xavier Lauth, Janet Trowbridge, Jennifer Rudisill, Robert A. Dorschner, Vasumati Pestonjamasp & Richard L. Gallo

  4. Division of Neonatology, Massachusetts General Hospital, Boston, 02114, Massachusetts, USA

    Joseph Piraino & Kenneth Huttner

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Correspondence to Richard L. Gallo.

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Nizet, V., Ohtake, T., Lauth, X. et al. Innate antimicrobial peptide protects the skin from invasive bacterial infection. Nature 414, 454–457 (2001). https://doi.org/10.1038/35106587

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